Contact PD/PI: Laskowitz, Daniel ABSTRACT Spontaneous intracerebral hemorrhage (ICH) remains a devastating stroke subtype, affecting as many as 80,000 people annually in the United States and associated with high mortality. At present, neither mortality nor neurological function are improved by any studied intervention, which have primarily focused on reducing hematoma volume. However, much of the neuronal cell death after ICH occurs through secondary injury mechanisms. Following initial injury, development of cerebral edema, subsequent intracranial hypertension, and ultimately cell death are mediated by brain inflammatory responses. Controlling this inflammatory response may mitigate brain damage and result in improved outcomes. AegisCN has developed a novel, proprietary, neuroprotective drug, CN-105, that demonstrates robust anti-inflammatory activity, and reduces cerebral edema and neuronal cell death in vitro and in vivo. CN105 has an outstanding safety profile (as confirmed by preclinical toxicity studies and Phase 1 clinical study results), excellent pharmacokinetics, small molecule size resulting in a well-documented ability to penetrate the blood brain barrier, an attractive half-life for dosing purposes and a long-lasting therapeutic effect. The objective of this proof of principle proposal is to evaluate the safety and feasibility of IV administration of CN-105, delivered every 6 hours for 72 hours in patients with acute supratentorial ICH. If successful, these data would lead to the development of clinical trials demonstrating the efficacy of CN-105 after ICH. Ultimately, our work would represent the first pharmacological intervention to improve outcome after ICH.